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1.  Quantitative correlation between penicillin resistance and beta-lactamase activity specified by the R plasmids R1, R1 bla-45, and RP1 in Escherichia coli K-12. 
A mutant of the R plasmid R1 which synthesizes a beta-lactamase with altered kinetic characteristics was isolated. The level of penicillin resistance specified by this plasmid was correctly predicted from the properties of the wild-type R1 according to a simple theoretical model published by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368--372, 1977). The model also accounts for the high level of penicillin resistance specified by the R plasmid RP1.
PMCID: PMC284074  PMID: 7004346
2.  Growth and antifungal homoazasterol production in Geotrichum flavo-brunneum. 
The growth cycle and production of 15-aza-24-methylene-8, 14-cholestadiene-3 beta-ol (15-azasterol) in Geotrichum flavo-brunneum strain NRRL28804 have been studied. During the growth cycle of this organism, morphological changes were noted which corresponded to changes in the pH of the culture medium. A physiological shift from acid to base production also occurred during the growth cycle. Concomitant with this physiological shift was the synthesis of 15-azasterol. Upon synthesis of this azasterol, variations in the sterol pool were observed. These variations are identical to sterol alterations in susceptible yeast cells exposed to this drug (P. R. Hays, W. D. Neal, and L. W. Parks, Antimicrob. Agents Chemother. 12: 185-191, 1977.) It appears that NRRL28804 avoids growth inhibition from 15-azasterol by confining its production to late in the growth cycle.
PMCID: PMC284097  PMID: 7192535
3.  Influence of chemical modification of N alpha-cocoyl-L-arginine ethyl ester on its hepatitis B surface antigen-inactivating effect. 
We have reported previously that N alpha-cocoyl-L-arginine ethyl ester (CAE) strongly inactivates hepatitis B surface antigen (HBsAg; Sugimoto and Toyoshima, Antimicrob. Agents Chemother. 16:329--332, 1979). Replacement of the L-arginine moiety of CAE by L-lysine did not decrease the HBsAg-inactivating effect of CAE, whereas replacement by some neutral amino acids and L-ornithine decreased it. Esterification of the carboxyl group of N alpha-acyl-L-arginine enhanced its inactivating effect. When the ethyl ester of CAE was converted to an amide group, the effect was appreciably decreased. Modification of the carboxyl group was essential for the inactivation. The effectiveness of N alpha-acyl-L-arginine ethyl ester depends upon the length of the acyl group, with the optimum length for the inactivation of HBsAg being C12 to C14. In addition to CAE, N alpha-lauroyl-L-lysine ethyl ester and N alpha-cocoyl-L-arginine amide were found to be strong inactivators of HBsAg. Significant inactivating effects on HBsAg were not observed in many anionic detergents containing an amino acid. These results suggest that for strongly inactivating HBsAg, a compound should contain a special amino acid, such as L-arginine, and a long acyl group and exhibit a cationic property.
PMCID: PMC284042  PMID: 7447415
4.  In vitro activities of cefotaxime and moxalactam (LY127935) against Haemophilus influenzae. 
The in vitro activities of two new beta-lactam antibiotics, cefotaxime and moxalactam (LY127935), were compared with those of cefamandole, cefoxitin, cefuroxime, and ampicillin against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae. Both cefotaxime and LY127935 were highly active against all isolates irrespective of beta-lactamase production.
PMCID: PMC283820  PMID: 6252832
5.  Radioimmunoassay of gentamicin in Micromonospora medium extracts. 
Medium extracts of Micromonospora adversely affected a radioimmunoassay which was used for the measurement of gentamicin in the medium. An overestmation or an underestimation resulted, as judged by the addition of extracts to a gentamicin standard sample.
PMCID: PMC283818  PMID: 7425609
6.  Hydrolysis of 3-acetoxymethyl cephalosporins by lysed whole blood. 
Cephalosporins having a 3-acetoxymethyl group are hydrolyzed to the corresponding desacetyl derivative by lysed whole blood but not by plasma or serum. When bioassays for this important class of cephalosporins must be run in whole blood or on tissues containing whole blood, steps should be taken to assure that the influence of the whole blood on the bioassay is properly interpreted.
PMCID: PMC283735  PMID: 7352755
7.  In Vitro Activity of Rosaramicin Against Chlamydia trachomatis 
In vitro, rosaramicin was highly active against Chlamydia trachomatis when added to the culture system 1 or 48 h after inoculation with the chlamydia.
PMCID: PMC353001  PMID: 7235684
8.  In vitro activity of Ro 13-9904, cefuroxime, cefoxitin, and ampicillin against Neisseria gonorrhoeae. 
In vitro susceptibilities of 87 isolates of non-penicillinase-producing Neisseria gonorrhoeae and 8 isolates of penicillinase-producing N. gonorrhoeae to Ro 13-9904, cefuroxime, cefoxitin, and ampicillin were determined. Ro 13-9904 was the most effective of the four drugs, inhibiting growth of both non-penicillinase-producing and penicillinase-producing N. gonorrhoeae.
PMCID: PMC283996  PMID: 6778381
9.  Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila. 
A total of 15 Legionella pneumophilia isolated were tested against 16 antimicrobial agents used singly and in combination with clavulanic acid. When combined with clavulanic acid, 4 of the 16 antimicrobial agents produced no enhanced effect. However, the minimal inhibitory concentrations of 12 of the antimicrobial agents were reduced by one-half to one-third when in combination with clavulanic acid. These reductions reflected only a one-dilution decrease, however, in the original minimal inhibitory concentrations. Thus, clavulanic acid combinations appear to be only nominally effective beta-lactamase inhibitors against L. pneumophilia.
PMCID: PMC283995  PMID: 6969575
10.  Bioassay for determination of vancomycin in the presence of rifampin or aminoglycosides. 
Vancomycin determinations were performed in the presence of an aminoglycoside or rifampin. A previously reported bioassay method was modified by using a rifampin-resistant strain and increasing the NaCl concentration in the minimal salts-glucose assay agar from 0.2 to 6.0%.
PMCID: PMC283860  PMID: 6772095
11.  Activity of beta-lactamase produced by Bacteroides fragilis against newly introduced cephalosporins. 
The purified beta-lactamase from Bacteroides fragilis hydrolyzed newly introduced cephalosporins including cefuroxime and HR 756, and was inhibited by 7 alpha-methoxylated cephalosporins such as 6059-S and YM09330.
PMCID: PMC283862  PMID: 6967295
12.  Inhibition of candidacidal activity of human neutrophil leukocytes by aminoglycoside antibiotics. 
We have tested the effect of five aminoglycoside antibiotics (gentamicin, sisomicin, tobramycin, ribostamycin, and amikacin) on the candidacidal activity of human neutrophils in vitro; all of them are inhibitory and can be grouped into three significantly different levels of toxicity. Gentamicin in the most toxic and sisomicin is the least toxic.
PMCID: PMC283731  PMID: 7352753
13.  MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities. 
The practical application of thienamycin, a novel beta-lactam antibiotic with a broad activity spectrum, was compromised by problems of instability. MK0787, N-formimidoyl thienamycin, does not have this liability. As reported, bacterial species resistant to most beta-lactam antibiotics, such as Pseudomonas aeurginosa, Serratis, Enterobacter, Enterococcus, and Bacteroides spp., are uniformly susceptible to MK0787, usually at one-half the inhibitory level of thienamycin. Bactericidal activity usually occurs at the minimal inhibitory concentration endpoint. Activity was reduced only at the highest inoculum densities tested and by a lessor factor than was observed with reference beta-lactam antibiotic active against P. aeruginosa and beta-lactamase-bearing strains. MK0787 exhibits a broad spectrum of in vivo activity when evaluated parenterally for efficacy against systemic infections in mice. The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference beta-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935.
PMCID: PMC283917  PMID: 6931549
14.  Cefoperazone (T-1551), a new semisynthetic cephalosporin: comparison with cephalothin and gentamicin. 
The in vitro activity of cefoperazone (T-1551) against almost 9,000 recent clinical isolates at six institutions was tested and compared with that of cephalothin and gentamicin. The modal minimum inhibitory concentrations of cefoperazone were 16- and 4-fold less than those of cephalothin and gentamicin, respectively, against 5,503 strains of Enterobacteriaceae. Species normally resistant to cephalothin, such as indole-positive protease and enterobacters, were almost universally susceptible to cefoperazone. Cefoperazone demonstrated activity comparable to gentamicin against Pseudomonas aeruginosa and other pseudomonads.
PMCID: PMC283865  PMID: 6446879
15.  Rise and fall of shigella antibiotic resistance. 
Ampicillin resistance of shigellae first appeared in Omaha in 1971, peaked at 68% between 1973 and 1974, and declined to 7% between 1977 and 1978. This reflected the rise and fall of strains with nine different multiple antibiotic resistance patterns that included ampicillin.
PMCID: PMC283736  PMID: 6898151
16.  Cefoperazone concentrations in bile and gall bladder wall after intravenous administration. 
Cefoperazone concentrations in the common duct bile, gall bladder bile, and gall bladder wall were determined in four patients with cholelithiasis and one patient with carcinoma of the head of the pancreas, all of whom had normal renal functions. Within 65 min after a 1-g intravenous administration, maximum concentrations ranged from 373.4 to 3,100 micrograms/ml in common duct bile and from 6.8 to 680 micrograms/ml in gall bladder bile. Cefoperazone concentrations per gram of the gall bladder wall ranged from 16.8 to 48.0 micrograms.
PMCID: PMC353002  PMID: 6453556
17.  Killing of oxacillin-exposed staphylococci in human polymorphonuclear leukocytes. 
Twelve strains of Staphylococcus aureus isolated from patients and two collection strains were grown on membranes placed on agar containing subminimal inhibitory concentrations of oxacillin. Clusters of staphylococci held together by thick cross walls resulted. These organisms, as well as the same strains grown in the same way on drug-free medium (control), were eluted from the membranes and were incubated with human polymorphonuclear leukocytes (PMNs) from various donors. Phagocytosis was comparable for both staphylococci exposed to oxacillin and control staphylococci, but the killing effect was different. The staphylococci grown on membranes in the presence of oxacillin were less susceptible to killing than the control staphylococci, but the killing effect was different. The staphylococci grown on membranes in the presence of oxacillin were less susceptible to killing than the control staphylococci. After 0.5 and 1 h of incubation with PMNs, the killing rates for oxacillin-grown versus control staphylococci were 52 and 70% and 65 and 85%, respectively (P < 0.01). After 2 and 3 h of incubation, the killing was similar. Most clusters of staphylococci contain a few individual cells that are located in the center of the cluster and are surrounded by other staphylococci; therefore, they are protected from adverse agents in the environment. This could explain why the phagocytized clusters are less susceptible than control staphylococci to the killing effect of PMNs during the first hour of incubation. Oxacillin does not penetrate into PMNs and in the absence of the drug the cross walls lyse, liberating the constituent staphylococci. This coincides with the increase in the percentage of cluster killing by PMNs after 2 and 3 h of incubation.
PMCID: PMC284095  PMID: 7447433
18.  Purification and biochemical properties of beta-lactamase produced by Proteus rettgeri. 
beta-Lactamase produced by Proteus rettgeri was found to be a typical cephalosporin beta-lactamase on the basis of its substrate hydrolysis profile. The enzyme activity was enhanced by prior treatment with an inducer. The enzyme was purified 166-fold by carboxymethyl-Sephadex column chromatography which indicated that its molecular weight was 42,000 +/- 2,000 and its isoelectric point was 8.7. Cefoperazone, cefoxitin, cefusulodin, cefmetazole, cefotaxime, 6059-S, FK749, YM-09330, carbenicillin, and cloxacillin were stable to this enzyme and possessed the function of competitive inhibition, as shown by their affinity for the beta-lactamase. The enzyme activity was inhibited by iodine, p-chloromerburibenzoate, and HG2+ ion. Clavulanic acid and CP-45899 displayed poor inhibitory activity toward this enzyme. The optimal pH was 8.0, and the optimal temperature was 50 degrees C.
PMCID: PMC284076  PMID: 6969578
19.  Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics. 
O-Demethylfortimicin A (compound A49759) was tested against 445 bacteria, and the results were compared with those obtained with fortimicin A, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin. A49759 was found to be active and bactericidal against the Enterobacteriaceae, nonfermentative gram-negative bacilli, and Staphylococcus aureus. A49759 was two- to fourfold more active than fortimicin A against most species tested, but generally fourfold less active than amikacin against this population of Pseudomonas aeruginosa (85% inhibited at less than or equal to 16 microgram of amikacin per ml and 85% inhibited at less than or equal to 64 microgram of A49759 per ml). Only amikacin and A49759 were resistant to most aminoglucoside-inactivating enzymes and also had significant antipseudomonal activity. Amikacin was inactivated by aminoglycoside 6'-acetyltransferase, and A49759 was inactivated by aminoglycoside 3-acetyltransferase. The minimal inhibitory concentrations of all tested aminoglycosides were increased by augmenting the inoculum size.
PMCID: PMC284090  PMID: 7447431
20.  In vitro activity of N-formimidoyl thienamycin (MK0787), a crystalline derivative of thienamycin. 
N-Formimidoyl thienamycin (MK0787) is a derivative of thienamycin, a unique, new beta-lactam antibiotic. Its activity against 285 aerobic and facultatively anaerobic clinical isolates was compared with the activities of cephalothin, ampicillin, penicillin G, ticarcillin, and tobramycin. All of the 285 isolates, with the exception of 1 Staphylococcus epidermidis isolate, were inhibited by a concentration of N-formimidoyl thienamycin of less than or equal to 8 micrograms/ml. More than 50% of all isolates were inhibited by the lowest concentration of N-formimidoyl thienamycin tested (0.125 micrograms/ml); 98% of Staphylococcus aureus and 80% of S. epidermidis isolates were inhibited by N-formimidoyl thienamycin at a concentration of 0.125 micrograms/ml. Only 2 of 45 enterococci were not inhibited by 1 microgram of N-formimidoyl thienamycin per ml, and this drug was the most active agent tested against 162 gram-negative bacilli. It inhibited more than 95% of the gram-negative isolates at a concentration of less than or equal to 2 micrograms/ml. N-Formimidoyl thienamycin was as active or more active than tobramycin against Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis and substantially more active than ticarcillin. All 16 isolates of Klebsiella pneumoniae were inhibited by less than or equal to 0.5 micrograms of N-formimidoyl thienamycin per ml. The marked in vitro activity of this drug against a wide variety of clinical isolates makes it a promising new antibiotic.
PMCID: PMC284048  PMID: 6934707
21.  Therapeutic effects of cefotiam and cefazolin on experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. 
The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and cefazolin of short and long duration and starting at three different times (3, 18, and 30h) after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. With each of the multiday regimens there was a large segment of the day when plasma levels fell below assayable concentrations. In all cases, cefotiam proved about eight times as active as cefazolin, indicating that the potent in vitro antibacterial activity of cefotiam was well reflected in the therapeutic effect in this model infection. As judged by the total dose administered, the regimen of cefotiam producing a low but sustained plasma level gave better therapeutic effects than that exhibiting a high but transient plasma level. The cefotiam levels in the plasma of mice that received the regimen effective when initiated at 18 h after infection were less than the expected levels in humans after intravenous infusion of the usual clinical dose.
PMCID: PMC284047  PMID: 7004342
22.  Lack of toxicity of acyclovir to granulocyte progenitor cells in vitro. 
Granulocyte progenitor cells were grown with acyclovir to study potential marrow toxicity. Concentrations of up to 220 microM had little effect on progenitor cell growth.
PMCID: PMC284024  PMID: 7425614
23.  Phlebitis induced by parenteral treatment with flucloxacillin and cloxacillin: a double-blind study. 
Two studies were performed on a total of 54 patients with staphylococcal infections. Study I compares with phlebitogenic properties of flucloxacillin after intravenous infusions when either saline or sterile water was used as a solvent. No difference was observed between the two solvents, and the frequency of phlebitis for the total material without respect to solvents was 5% after 1 day of treatment and 13% after 2 days. Study II was a double-blind comparison of phlebitis caused by intravenous infusions of either flucloxacillin or cloxacillin. The frequencies of phlebitis were found to be 18 and 13%, respectively. After 2 days of treatment the frequency of phlebitis increased dramatically for both drugs. All infusions were given through a plastic cannula of 5-cm length and 1.2-mm diameter.
PMCID: PMC283994  PMID: 7447412
24.  Beta-lactamase-producing isolates of Bacteroides species from children. 
Two hundred twenty-four isolates of Bacteroides sp. were recovered from recurrently inflamed tonsils, infected peritoneal fluid, abscesses, wounds, and burns of hospitalized children. Isolates were examined for beta-lactamase production by the chromogenic cephalosporin analog 87/312 methodology. Altogether, 119 isolates were beta-lactamase producers. Of these, 53 were in the B. fragilis group, 28 were in the B. melaninogenicus groups, 12 were B. oralis, 4 were B. ruminicola subsp. brevis, and 22 were Bacteroides sp. Of 28 beta-lactamase-producing strains of B. melaninogenicus, 25 were recovered from tonsils. These observations indicate that in pediatric patients there is a significant incidence of beta-lactamase producers among anaerobes other than B. fragilis.
PMCID: PMC283957  PMID: 6968177
25.  Affinity of cefoperazone for penicillin-binding proteins. 
Cefoperazone (T-1551, CFP) a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. We investigated the affinity of CFP to penicillin-binding proteins (PBPs) and the inhibition of peptidoglycan synthesis by CFP. CFP had high affinities for Escherichia coli PBP-3, -1Bs, -2, and -1A, in descending order, and low affinities for PBP-4, -5, and -6. Similarly, CFP showed high affinity for Pseudomonas aeruginosa PBP-3, -1A, -1B, -2, and -4, in descending order. It is known that E. coli PBP-3 and P. aeruginosa PBP-3 participate in cell division. These results are in good agreement with the formation of filamentous cells of E. coli and P. aeruginosa treated with CFP. CFP had lower inhibitory activities on D-alanine carboxypeptidase IA and IB of E. coli than that of penicillin G, but its inhibitory activities on the cross-link formation in peptidoglycan synthesis were the same as those of penicillin G and higher than those of ampicillin.
PMCID: PMC283963  PMID: 6448021

Results 1-25 (377)